ArticleProceedings of the National Academy of Sciences of the United States of America2000
Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 147 citations in OpenAlex.
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- αeLife · 2023Article
- Rapid Pacing Decreases L-type CaThe Journal of membrane biology · 2023Article
- Role of CaArchives of toxicology · 2023Review
- Modulation of L-type calcium channels in Alzheimer's disease: A potential therapeutic target.Computational and structural biotechnology journal · 2023Review
- Cardiac function, structural, and electrical remodeling by microgravity exposure.American journal of physiology. Heart and circulatory physiology · 2023Review
- PKC regulation of ion channels: The involvement of PIPThe Journal of biological chemistry · 2022Review
- PKCβ/NF-κB pathway in diabetic atrial remodeling.Journal of physiology and biochemistry · 2020Article
- Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins.Pflugers Archiv : European journal of physiology · 2020Review
- Article
- LITAF (Lipopolysaccharide-Induced Tumor Necrosis Factor) Regulates Cardiac L-Type Calcium Channels by Modulating NEDD (Neural Precursor Cell Expressed Developmentally Downregulated Protein) 4-1 Ubiquitin Ligase.Circulation. Genomic and precision medicine · 2019Article
- Association between ibrutinib and mid-cavitary Takotsubo cardiomyopathy: a case report and a review of chemotherapy-induced Takostubo's cardiomyopathy.European heart journal. Case reports · 2017Article
- Protein kinase C enhances plasma membrane expression of cardiac L-type calcium channel, CaChannels (Austin, Tex.) · 2017Article
- Redox regulation of the actin cytoskeleton and its role in the vascular system.Free radical biology & medicine · 2017Review
- M3 cholinoreceptors alter electrical activity of rat left atrium via suppression of L-type CaJournal of physiology and biochemistry · 2017Article
- Similar molecular determinants on Rem mediate two distinct modes of inhibition of CaChannels (Austin, Tex.) · 2016Article
- Phosphorylation of residues inside the SNARE complex suppresses secretory vesicle fusion.The EMBO journal · 2016Article
- Contribution of protein kinase Cα in the stimulation of insulin by the down-regulation of Cavβ subunits.Endocrine · 2014Article
- Calcineurin-dependent ion channel regulation in heart.Trends in cardiovascular medicine · 2014Review
- PKC independent inhibition of voltage gated calcium channels by volatile anesthetics in freshly isolated vascular myocytes from the aorta.Cell calcium · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have investigated the mechanism underlying the modulation of the cardiac L-type Ca(2+) current by protein kinase C (PKC). Using the patch-clamp technique, we found that PKC activation by 4-alpha-phorbol 12-myristate 13-acetate (PMA) or rac-1-oleyl-2-acetylglycerol (OAG) caused a substantial reduction in Ba(2+) current through Ca(v)1.2 channels composed of alpha(1)1.2, beta(1b), and alpha(2)delta(1) subunits expressed in tsA-201 cells. In contrast, Ba(2+) current through a cloned brain isoform of the Ca(v)1.2 channel (rbC-II) was unaffected by PKC activation. Two potential sites of PKC phosphorylation are present at positions 27 and 31 in the cardiac form of Ca(v)1.2, but not in the brain form. Deletion of N-terminal residues 2-46 prevented PKC inhibition. Conversion of the threonines at positions 27 and 31 to alanine also abolished the PKC sensitivity of Ca(v)1.2. Mutant Ca(v)1.2 channels in which the threonines were converted singly to alanines were also insensitive to PKC modulation, suggesting that phosphorylation of both residues is required for PKC-dependent modulation. Consistent with this, mutating each of the threonines individually to aspartate in separate mutants restored the PKC sensitivity of Ca(v)1.2, indicating that a change in net charge by phosphorylation of both sites is responsible for inhibition. Our results define the molecular basis for inhibition of cardiac Ca(v)1.2 channels by the PKC pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.